The intent of this project is to apply chemical oligonucleotide synthesis, recombinant DNA technology, and cell biology techniques to the isolation, analysis, and characterization of normal genes corresponding to genetic diseases. The enzymes phenylalanine hydroxylase and hypoxanthine guanine phosphoribosyl transferase have been isolated in order to obtain amino acid sequencing information. Chemical synthesis of oligonucleotides has been established. An octadecanucleotide complementary to a protion of the human Beta-globin mRNA has been synthesized for use in analysis of Beta-globin regulation. Eight pentadecanucleotides which potentially complement a portion of the mRNA encoding rat phenylalanine hydroxylase have also been synthesized. Total cell mRNA has been prepared from rat liver, human reticulocytes, mouse, and hybrid (human/mouse) cells.